Evaluation of hemostasis in patients with end-stage renal disease

Abstract

An increased bleeding risk is reported for patients with end-stage renal disease. This study aims to analyze, whether bleeding risk can be assessed by global tests of hemostasis. Standard laboratory tests and an extended evaluation of hemostasis by rotational thromboelastometry, platelet function analyzer (PFA) and multiple electrode aggregometry as well as thrombin generation assays and measurement of fibrinolytic potential were performed in 20 patients on hemodialysis, 10 patients on peritoneal dialysis, 10 patients with chronic kidney disease stage G5 (CKD5) and in 10 healthy controls (HC). Hemoglobin was significantly lower in patients with end-stage renal disease versus HC (each p<0.01). Patients on peritoneal dialysis showed increased fibrinogen levels compared to HC (p<0.01), which were also reflected by FIBTEM results (each p<0.05). 41% of hemodialysis patients and 44% of CKD5 patients presented with prolonged PFA-ADP-test (p<0.05), while no patient on peritoneal dialysis and no HC offered this modification. Thrombin generating potential was significantly lower in patients on hemodialysis, while clot lysis time revealed a hypofibrinolytic state in patients on hemo- and peritoneal dialysis compared to HC (p<0.001). In conclusion, patients with end-stage renal disease have complex hemostatic changes with both hyper- and hypocoagulable features, which are dependent on use and type of dialysis. Hypercoagulable features include elevated fibrinogen levels and a hypofibrinolytic state, whereas hypocoagulable features include decreased thrombin generating capacity and platelet dysfunction. Our results may contribute to a more rational approach to hemostatic management in these patients.

Fig 1. Creatinine and blood urea nitrogen.

Values are given as mean ± standard error of the mean for each group. Dotted lines mark upper normal range. **p < 0.01 vs. HC; ***p < 0.001 vs. HC. HC healthy control, CKD5 patients with chronic kidney disease stage G5, HD patients on hemodialysis, PD patients on peritoneal dialysis.

Fig 2. Fibrinogen.

Values are given as mean ± standard error of the mean for each group. Dotted line marks upper normal range. **p < 0.01 vs. HC. HC healthy control, CKD5 patients with chronic kidney disease stage G5, HD patients on hemodialysis, PD patients on peritoneal dialysis.

Fig 3. Platelet function analyzer.

The platelet function analyzer (PFA) test measured platelet aggregate formation under high shear rates and with addition of either collagen/epinephrine (A) or collagen/adenosine diphosphate (B) as agonists. Lines indicate mean ± standard error of the mean for each group. Dotted lines mark upper normal range. *p < 0.05 vs. HC; ##p < 0.01 vs. PD. HC healthy control, CKD5 patients with chronic kidney disease stage G5, HD patients on hemodialysis, PD patients on peritoneal dialysis.

Fig 4. Clotting time measured by rotational thromboelastometry.

Clotting time in INTEM (A) corresponds to activated partial thrombin time. Clotting time in INTEM was not prolonged in any patient. Clotting time in EXTEM (B) corresponds to prothrombin time. A strongly prolonged clotting time in EXTEM was found in one patient of every group, except HC with all other measured parameters being unchanged. No differences between groups were detected. Lines indicate mean ± standard error of the mean for each group. Dotted lines indicate normal range. HC healthy control, CKD5 patients with chronic kidney disease stage G5, HD patients on hemodialysis, PD patients on peritoneal dialysis.

Fig 5. Maximum clot firmness measured by rotational thromboelastometry (FIBTEM).

FIBTEM reflects the plasmatic part of clot firmness. Clot firmness tended to be increased in patients with end-stage renal disease becoming significant for PD patients. *p < 0.05 vs. HC. Lines indicate mean ± standard error of the mean for each group. Dotted lines indicate normal range. HC healthy control, CKD5 patients with chronic kidney disease stage G5, HD patients on hemodialysis, PD patients on peritoneal dialysis.

Fig 6. Results of multiple electrode aggregometry.

ADPtest (A) reflects function of the P₂Y₁₂ and GpIIb/IIIa receptor. ASPItest (B) reflects function of the platelet cyclooxygenase and the GpIIb/IIIa receptor. TRAPtest (C) reflects function of the protease-activated receptor 1 and the GpIIb/IIIa receptor. RISTOlowTest (D) reflects function of von Willebrand Factor. No significant differences between groups were detected. Lines indicate mean ± standard error of the mean for each group. Dotted lines indicate normal range. HC healthy control, CKD5 patients with chronic kidney disease stage G5, HD patients on hemodialysis, PD patients on peritoneal dialysis.

Fig 7. Results of thrombin generation assays.

Data are given as medians with interquartile ranges. *p < 0.05 and ***p < 0.001 vs. HC. HC healthy control, CKD5 patients with chronic kidney disease stage G5, HD patients on hemodialysis, PD patients on peritoneal dialysis.

Fig 8. Clot lysis time.

Data are given as medians with interquartile ranges. ***p < 0.001 vs. HC. HC healthy control, CKD5 patients with chronic kidney disease stage G5, HD patients on hemodialysis, PD patients on peritoneal dialysis.